MIT Scientists Develop Improved CRISPR-Cas9 For Gene Editing

Researchers at the Massachusetts Institute of Technology (MIT) have developed an improved CRISPR gene editing tool that makes it possible to more precisely and efficiently target a DNA’s modification. Findings of the study were published Tuesday in the journal Science. The new, improved CRISPR-Cas9 system dramatically reduces the possibility of potentially dangerous “off-target” edits.

What is the CRISPR system?

The ability to edit genes of living beings could allow researchers to correct defects in human genes, opening new avenues of treating critical diseases. However, it could also be used to create “designer babies.” That’s why it has raised various ethical concerns, with some critics calling for a worldwide ban on genetic modification of human embryos. Experts have gathered in Washington to discuss how the revolutionary technology could be used ethically.

CRISPR-Cas9 consists of two components. First, an enzyme called Cas9 acts as biological “scissors” that captures the target DNA and cuts it into two. Second is a guide RNA that tells Cas9 exactly what to do and where to cut. It’s a method borrowed from nature. Bacteria have long been using it to protect themselves against foreign DNA from viruses.

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Replacing three positively-charged amino acids did the trick

Scientists have been using the system in the lab to cut out defective DNA in human cells that cause diseases. Though it is effective and easy to use, a major problem with CRISPR is that, once it gets inside the cell, it could cut out even non-targeted sites on the genome, which could lead to life-threatening diseases including cancer. The MIT team led by Feng Zhang of the Broad Institute has re-engineered the Cas9 enzyme such that it reduces the off-target editing to “undetectable levels.”

Zhang and his colleagues essentially replaced 3 positively-charged amino acids in the Cas9 enzyme with neutral ones to achieve this. The modified enzyme called eSpCas9 will help in DNA editing applications that require highly specific details. CRISPR has been used in several fields including engineering mosquitoes that can’t spread malaria.

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